Efficacy and safety of Ex-PRESS® mini shunt surgery versus trabeculectomy for neovascular glaucoma: a retrospective comparative study.

BACKGROUND: The objective of this study is to evaluate and compare the short-term efficacy and safety of Ex-PRESS® mini shunt surgery and trabeculectomy for neovascular glaucoma (NVG). METHODS: Patients with NVG who underwent Ex-PRESS® mini shunt surgery or trabeculectomy as a primary glaucoma surgery between March 2013 and October 2015 were included in the study, and their medical charts were retrospectively reviewed. The Ex-PRESS® and trabeculectomy groups included 14 eyes and 30 eyes, respectively. Surgical failure was defined by an intraocular pressure (IOP) of ≥21 mmHg (condition A) or ≥ 18 mmHg (condition B); Kaplan-Meier survival analyses and the multivariable Cox proportional hazards model were used to assess efficacies. RESULTS: Kaplan-Meier survival analyses indicated that the probabilities of success at 1 year for the Ex-PRESS® group were 25.7 and 31.8% based on complete and qualified success under condition A, respectively. The corresponding values for the trabeculectomy group were 47.8 and 69.3%, and there was a significant difference in qualified success with condition A (Fig. 1; P = 0.018), while there were no significant differences in the other criteria. Ex-PRESS® mini shunt surgery and higher intraocular pressure were independent prognostic factors using Cox proportional hazards model analyses in qualified success as in condition A (P = 0.012 and 0.0495, respectively). The occurrences of postsurgical hyphema and bleb leaks were significantly higher in the trabeculectomy group (P = 0.005 and 0.008, respectively). CONCLUSION: During a 1 year follow-up, Ex-PRESS® mini shunt surgery was a less effective, but safer treatment for NVG compared with trabeculectomy.

Decreased MCP-1/CCR2 axis-mediated chemotactic effect of conjunctival fibroblasts after transdifferentiation into myofibroblasts.

The purpose of this study is to investigate the change in chemotactic effects of human conjunctival fibroblasts (HConFs) after transdifferentiation into myofibroblasts, and to explore related molecular mechanisms. HConFs were treated with 5 ng/mL transforming growth factor (TGF)-ß2 for 48 h to induce transdifferentiation into myofibroblasts. The cytokine concentrations in the conditioned media of HConFs were measured by multiplex bead-based immunoassays. The Boyden chamber assay was used to assess the chemotactic effects using the monocyte cell line, THP-1 cells. The concentration of monocyte chemoattractant protein (MCP)-1 in the conditioned media was decreased after transdifferentiation into myofibroblasts (P < 0.001). The conditioned media of HConFs exerted a chemotactic effect on THP-1 cells, but this effect decreased after transdifferentiation into myofibroblasts (P = 0.032). The number of migrated THP-1 cells decreased significantly upon treatment with neutralizing anti-MCP-1 antibodies (P = 0.006) and tended to decrease upon treatment with C-C chemokine receptor (CCR) 2 antagonist. The chemotactic effect of HConFs mediated by the MCP-1/CCR2 axis was decreased after transdifferentiation into myofibroblasts.

Postoperative Changes in Aqueous Monocyte Chemotactic Protein-1 Levels and Bleb Morphology after Trabeculectomy vs. Ex-PRESS Shunt Surgery.

PURPOSE: To evaluate the postoperative changes in blebs and levels of aqueous monocyte chemotactic protein-1 (MCP-1) after trabeculectomy vs. Ex-PRESS tube shunt surgery. METHODS: Rabbits were subjected to trabeculectomy or Ex-PRESS tube shunt surgery and observed for up to 3 months. Intraocular pressure (IOP) was measured using a rebound tonometer. The MCP-1 level was measured by enzyme-linked immunosorbent assay (ELISA). Bleb morphology was evaluated using photos and anterior-segment optical coherence tomography (OCT). RESULTS: There were no differences in bleb appearance or IOP at any time between the groups. Bleb wall density in the anterior-segment OCT image was significantly lower 1 week after surgery in the Ex-PRESS group than the trabeculectomy group. The MCP-1 level in control eyes was 304.1 ± 45.2 pg/mL. In the trabeculectomy group, the mean aqueous MCP-1 level was 1444.9, 1914.3, 1899.8, 516.4, 398.3, 427.3, 609.5, 1612.7, 386.2, and 167.9 pg/mL at 3, 6, and 12 h, and 1, 2, 5, 7, 14, 30, and 90 days after surgery, respectively. In the Ex-PRESS group, the corresponding values were 1744.0, 1372.0, 932.5, 711.7, 396.1, 487.3, 799.5, 1327.9, 293.6, and 184.0 pg/mL. There were no significant differences in the aqueous MCP-1 level between the groups at any time point. CONCLUSION: The postoperative changes were similar in the Ex-PRESS and trabeculectomy groups, except for bleb wall density in the anterior-segment OCT image. The postoperative aqueous MCP-1 level had bimodal peaks in both groups.

Simultaneous increase in multiple proinflammatory cytokines in the aqueous humor in neovascular glaucoma with and without intravitreal bevacizumab injection.

PURPOSE: To investigate aqueous humor proinflammatory cytokine levels of patients with neovascular glaucoma (NVG), and to analyze the effects of background factors in the expression of these molecules. METHODS: This cross-sectional study enrolled 137 participants who were grouped into (1) primary open-angle glaucoma (POAG; n = 36) patients; (2) NVG patients (NVG; n = 33); and (3) cataract surgery patients as a comparative group (CG; n = 68). Aqueous humor samples were collected from the anterior chamber at the start of surgery, deposited in CryoTubes, registered, and stored at -80 °C until processing. Multiplex microparticle-based immunodetection was performed by using xMAP and the Human Cytokine/Chemokine Panel I. Bevacizumab was injected into the vitreous cavity 1 to 2 days before surgery in 22 NVG patients (IVB group), whereas 11 NVG patients received no antivascular endothelial growth factor (VEGF) therapy 3 months preoperatively (N group). The Wilcoxon rank sum test or Fisher's exact test for two variables and the Tukey-Kramer honestly significant difference test for multiple variables were used to compare the cytokine levels. RESULTS: The NVG patients had higher levels of interleukin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, tumor necrosis factor-α (TNF-α), and platelet-derived growth factor (PDGF)-AA compared to both the CG and POAG groups. The levels of IL-6, IL-8, MCP-1, and PDGF-AB/BB were higher in the IVB group than the N group, whereas the VEGF level was significantly lower in the IVB group (P < 0.01). CONCLUSIONS: Intravitreal bevacizumab injection decreased VEGF levels, but not those of the other cytokines.

Fornix-based versus limbal-based conjunctival flaps in trabeculectomy with mitomycin C in high-risk patients.

PURPOSE: To compare the surgical outcomes of limbal-based and fornix-based trabeculectomy in eyes with a history of ocular incisional surgery. METHODS: Twenty-six eyes underwent limbal-based trabeculectomy (group LB), and were condition matched with 26 eyes that received fornix-based trabeculectomy (group FB). Surgical failure was recorded retrospectively if the intraocular pressure value was either ≥21, ≥18, and ≥15 mmHg (conditions A, B, and C, respectively) or <4 mmHg or if the patient required additional glaucoma surgery. Kaplan-Meier survival curve analysis was used to assess surgical failure. RESULTS: For condition A, the 2 year surgical success probabilities were 75.0% and 63.9% in groups FB and LB, respectively (P=0.124). The corresponding values were 55.0% and 61.7% (P=0.638) in condition B, and 55.0% and 57.0% (P=0.454) in condition C. The rates of bleb leakage, hypotony, choroidal detachment, and bleb-related infection were 11.5%, 26.9%, 50.0%, and 7.7% in group LB, respectively. The corresponding values in group FB were 30.8%, 23.1%, 46.2%, and 0.0%, which were not statistically different between the two groups. CONCLUSION: No significant differences in surgical outcomes were observed between limbal-based and fornix-based trabeculectomy for patients with a history of incisional ocular surgeries.

Risk factors for hyphema after trabeculectomy with mitomycin C.

PURPOSE: To determine the risk factors for hyphema after trabeculectomy with mitomycin C (MMC). PATIENTS AND METHODS: In total, 420 patients (420 eyes) with glaucoma who underwent trabeculectomy with MMC between June 1, 2005 and December 31, 2010 at Kumamoto University Hospital, Japan, were retrospectively evaluated. Hyphema after trabeculectomy was defined as the niveau formed by bleeding in the anterior chamber. Logistic multivariable analysis was applied to determine the risk factors for hyphema. RESULTS: Of the 420 patients, 104 (24.8%) had hyphema. Neovascular glaucoma [NVG; odds ratio (OR)=2.404; P=0.0017] and anticoagulant or antiplatelet medication at trabeculectomy (OR=2.143; P=0.0274) were significant risk factors for hyphema. Of the 108 NVG patients, 43 (39.8%) had hyphema after trabeculectomy with MMC. In the subgroup analysis of NVG patients, neovascularization in the anterior chamber angle at trabeculectomy (OR=5.7886; P=0.0163) and anticoagulant or antiplatelet medication at trabeculectomy (OR=3.3325; P=0.0450) were risk factors for hyphema, whereas preoperative intravitreal bevacizumab injection significantly reduced the hyphema risk (OR=0.3568; P=0.0275). CONCLUSIONS: The risk factors for hyphema after trabeculectomy with MMC are independently associated with NVG and anticoagulant or antiplatelet medication. Neovascularization in the anterior chamber at trabeculectomy and anticoagulant or antiplatelet medication enhance the risk of hyphema developing in NVG patients, whereas preoperative injection of intravitreal bevacizumab reduces the likelihood.

Risk factors for choroidal detachment after trabeculectomy with mitomycin C.

PURPOSE: To evaluate the risk factors for choroidal detachment after trabeculectomy with mitomycin C (MMC). MATERIALS AND METHODS: We retrospectively evaluated 420 patients (420 eyes) with glaucoma who underwent trabeculectomy with MMC between June 1, 2005 and December 31, 2010 at Kumamoto University Hospital, Japan. Choroidal detachment after trabeculectomy was defined as a solid-appearing elevation of the retina and choroid. Logistic multivariable analysis was applied to determine the risk factors for choroidal detachment. The following factors were assessed: gender, age, subtypes of glaucoma, eye laterality, history of previous cataract surgery, preoperative intraocular pressure (IOP; mean of three Goldmann applanation readings recorded on different days), postoperative IOP (mean of seven Goldmann applanation readings recorded on 7 consecutive days after trabeculectomy), and postoperative laser suture lysis. RESULTS: Of the 420 patients, 79 (18.8%) revealed choroidal detachments. The mean period between trabeculectomy and choroidal detachment was 6.1 ± 3.6 days. The mean IOP at the time of the choroidal detachment was 5.5 ± 3.6 mmHg. Age (odds ratio [OR] = 1.028/year, P = 0.0068) and postoperative IOP (OR = 0.887/mmHg, P < 0.0001) were risk factors for choroidal detachment after trabeculectomy. The subgroup analysis for eyes with open angle glaucoma (201 patients) revealed that age (OR = 1.060/year, P = 0.0040) and postoperative IOP (OR = 0.898/mmHg, P = 0.0110) were significant risk factors for choroidal detachment after trabeculectomy with MMC. CONCLUSION: Among glaucoma patients, older age and lower postoperative IOP are risk factors for choroidal detachment after trabeculectomy with MMC. In eyes with open angle glaucoma, older age and lower postoperative IOP are risk factors for choroidal detachment after trabeculectomy with MMC.

Elevated levels of monocyte chemoattractant protein-1 in the aqueous humor after phacoemulsification.

PURPOSE: To elucidate the impact of phacoemulsification on aqueous monocyte chemoattractant protein-1 (MCP-1) levels, and identify its cell origin. METHODS: For clinical study, aqueous humor samples were collected before and after surgery (17.0 ± 4.0 months postoperatively) from 21 cataract cases that underwent phacoemulsification and intraocular lens (IOL) implantation. Aqueous MCP-1 levels were determined using a multiplex immunoassay. For animal experiments, rabbits underwent phacoemulsification (± IOL). Aqueous humor samples were collected from nonoperated eyes and operated eyes, and immunoassays were performed. Eyes were analyzed by reverse transcription-polymerase chain reaction and immunohistochemical studies. RESULTS: In the clinical study, mean (± SD) aqueous MCP-1 levels were higher postoperatively (1773.5 ± 321.2 pg/mL) than preoperatively (796.9 ± 211.3 pg/mL; P < 0.0001). In animal experiments, mean aqueous MCP-1 levels (pg/mL) were higher in postoperative eyes on day 30 (207.1 ± 62.9) than in nonoperated eyes (31.2 ± 12.5; P = 0.018). IOL implantation did not affect the changes in MCP-1 levels. After phacoemulsification, MCP-1 mRNA expression was increased in the cornea, iris, ciliary body, and capsular bag. Expression of MCP-1 mRNA in the capsular bag, but not the other tissues, increased from day 30 to 90. Immunohistochemical studies showed positive immunoreactivity for MCP-1 in cells of the posterior capsule after phacoemulsification. CONCLUSIONS: aqueous MCP-1 levels were elevated in both human and animal eyes after phacoemulsification. Proliferated Lens epithelial cells on the capsule might be the major cell origin for prolonged MCP-1 production after phacoemulsification. (http://www.umin.ac.jp/ number, UMIN000005788.).